SARS-CoV-2 inhibitors - artificial compounds

Abstract

The invention discloses a compound with the general formula (I) wherein R1 to R6 are identical or not and are H, OH—, or OR7, wherein R7 is a C1 to C3 alkyl group or a C1 to C4 acyl group, with the proviso that at least four of R1 to R6 are different than H, for use in the treatment and prevention of COVID-19 in a human subject, especially for inhibiting SARS-CoV-2.

1 . A preparation comprising 3,3′,4,4′,5,5′-Hexahydroxystilbene 
       
         
           
           
               
               
           
         
       
       for use in the treatment and prevention of COVID-19 in a human subject, specifically for inhibiting SARS-CoV-2. 
     
     
         2 . The preparation or use according to  claim 1 , wherein the 3,3′,4,4′,5,5′-Hexahydroxystilbene is formulated into an amount that is effective for at least one of: inhibiting SARS-CoV-2 is inhibiting replication of SARS-CoV-2, for preventing the cytopathic effect of an active virus replication of SARS-CoV-2, or preventing viral infections with SARS-CoV-2 through airborne channels. 
     
     
         3 . The preparation according to  claim 1 , wherein the 3,3′,4,4′,5,5′-Hexahydroxystilbene is 3,3′,4,4′,5,5′-Hexahydroxy-trans-stilbene as an active ingredient in a pharmaceutically acceptable excipient. 
     
     
         4 . The preparation according to  claim 3 , wherein the preparation is for oral, sublingual, intramuscular, subcutaneous, nasal, oral mucosa, bronchial, pulmonary, skin, peritoneum or rectum administration, preferably for oral, sub-lingual or nasal administration. 
     
     
         5 . The preparation according to  claim 3 , wherein the preparation is provided as an inhalable and/or aerosol composition or as a nasal or oral spray and/or as sublingual films or tablets and/or as lollipops. 
     
     
         6 . The preparation according to  claim 1 , formulated for the treatment and prevention of COVID-19 in a human subject further comprising a pharmaceutically acceptable excipient selected from diluents, such as water, acetone, ethanol, polyethylene glycol, polypropylene glycol, 1,3-propanediol, butane-1,3-diol, isopropyl myristate, isopropyl palmitate, mineral oil, ethoxylated isostearyl alcohol, polyoxylated isostearyl alcohol, polyoxyethylene sorbitol fatty acid ester; carrier, such as glycerol, mannitol, sorbitol, xylitol, and erythritol absorbents, such as starch, dextrin, calcium sulfate, lactose, mannitol, sucrose, sodium chloride, glucose, urea, kaolin, microcrystalline cellulose, aluminium silicate; wetting agents and binders, such as water, glycerin, polyethylene glycol, ethanol, propanol, starch syrup, dextrin, syrup, honey, glucose solution, acacia syrup, gelatin syrup, sodium carboxymethyl cellulose, purple Gum, methyl cellulose, potassium phosphate, polyvinylpyrrolidone; disintegrants, such as dried starch, alginate, agar powder, alginate, sodium bicarbonate, calcium carbonate, polyoxyethylene sorbitol fat acid esters, sodium lauryl sulfonate, methyl cellulose, ethyl cellulose; disintegration inhibitors, such as sucrose, glyceryl tristearate, cocoa butter, hydrogenated oil; absorption enhancers, such as quaternary ammonium salts, sodium lauryl sulfate; lubricants, such as talc, silicon dioxide, corn starch, stearic acid, boric acid, liquid paraffin, polyethylene glycol; polyacrylic resins, liposomes, water-soluble carriers such as PEG4000 and PEG6000, PVP; antioxidants; pH buffers and/or salt buffers; solubility modulators; penetration enhancers; antioxidants, such as citric acid and its salts, tartaric acid and its salts, phosphoric acid and its salts, and ethylenediaminetetraacetic acid (EDTA) and its salts, vitamins C, E; or mixtures thereof. 
     
     
         7 . The preparation according to  claim 6 , wherein the preparation is an inhalation or aerosol preparation, an isotonic inhalation solution or suspension or a liquid or powdered aerosol. 
     
     
         8 . The preparation according to  claim 1 , wherein the 3,3′,4,4′,5,5′-Hexahydroxystilbene is formulated in an amount of from about 100 μg to about 10 g, in an amount of from about 1 mg to about 1 g, in an amount of from 10 mg to 500 mg, or in an amount of from about 20 mg to about 300 mg. 
     
     
         9 . The preparation of  claim 8 , wherein the preparation contains the 3,3′,4,4′,5,5′-Hexahydroxystilbene in an amount of from about 10 mg to about 1000 mg, in an amount of from about 25 mg to about 750 mg, in an amount of from 50 mg to 500 mg, or in an amount of from about 30 mg to about 100 mg. 
     
     
         10 . The pharmaceutical preparation of  claim 1 , wherein the preparation is contained in a metered dose inhaler, in a dry powder inhaler, or in a nebulizer. 
     
     
         11 . The pharmaceutical preparation of  claim 1 , wherein the preparation contains the compound in 0.001% to 50% w/v, in 0.01% to 20% w/v, in 0.1% to 20% w/v, or in 1% to 20% w/v. 
     
     
         12 . (canceled) 
     
     
         13 . (canceled) 
     
     
         14 . A method for the treatment and prevention of COVID-19 in a human subject, especially for inhibiting SARS-CoV-2 comprising administering to a subject infected by or are at risk of being infected by SARS-CoV-2 an effective amount of 3,3′,4,4′,5,5′-Hexahydroxystilbene or a pharmaceutical preparation thereof. 
     
     
         15 . The method of  claim 14 , wherein the 3,3′,4,4′,5,5′-Hexahydroxystilbene is 3,3′,4,4′,5,5′-Hexahydroxy-trans-stilbene and administered through airborne channels in a human subject. 
     
     
         16 . The method of  claim 14 , wherein the 3,3′,4,4′,5,5′-Hexahydroxystilbene at least one of: inhibits replication of SARS-CoV-2, prevents the cytopathic effect of an active virus replication of SARS-CoV-2, prevents viral infections with SARS-CoV-2 through airborne channels. 
     
     
         17 . The method of  claim 14 , wherein the 3,3′,4,4′,5,5′-Hexahydroxystilbene is an inhalation or aerosol preparation, an isotonic inhalation solution or suspension or a liquid or powdered aerosol. 
     
     
         18 . The method of  claim 14 , wherein the 3,3′,4,4′,5,5′-Hexahydroxystilbene is administered in an amount of from about 100 μg to about 10 g, in an amount of from about 1 mg to about 1 g, in an amount of from 10 mg to 500 mg, or in an amount of from about 20 mg to about 300 mg. 
     
     
         19 . The method of  claim 14 , wherein the 3,3′,4,4′,5,5′-Hexahydroxystilbene is administered in an amount of from about 10 mg to about 1000 mg, preferably in an amount of from about 25 mg to about 750 mg, more preferably in an amount of from 50 mg to 500 mg, even more preferably in an amount of from about 30 mg to about 100 mg. 
     
     
         20 . The method of  claim 14 , wherein the 3,3′,4,4′,5,5′-Hexahydroxystilbene is contained in a metered dose inhaler, in a dry powder inhaler, or in a nebulizer. 
     
     
         21 . The method of  claim 14 , wherein the 3,3′,4,4′,5,5′-Hexahydroxystilbene is in an amount between 0.001% to 50% w/v, between 0.01% to 20% w/v, between 0.1% to 20% w/v, or between 1% to 20% w/v.